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Your search keyword '"Zou, Xiangang"' showing total 3 results
Start Over Author "Zou, Xiangang" Topic cellular reprogramming
3 results on '"Zou, Xiangang"'

1. Establishment of porcine and human expanded potential stem cells.

Author

Gao X, Nowak-Imialek M, Chen X, Chen D, Herrmann D, Ruan D, Chen ACH, Eckersley-Maslin MA, Ahmad S, Lee YL, Kobayashi T, Ryan D, Zhong J, Zhu J, Wu J, Lan G, Petkov S, Yang J, Antunes L, Campos LS, Fu B, Wang S, Yong Y, Wang X, Xue SG, Ge L, Liu Z, Huang Y, Nie T, Li P, Wu D, Pei D, Zhang Y, Lu L, Yang F, Kimber SJ, Reik W, Zou X, Shang Z, Lai L, Surani A, Tam PPL, Ahmed A, Yeung WSB, Teichmann SA, Niemann H, and Liu P

Subjects
Animals, Blastomeres cytology, Blastomeres metabolism, Cell Lineage genetics, Embryonic Stem Cells cytology, Germ Layers growth & development, Germ Layers metabolism, Humans, Mice, Regenerative Medicine, Signal Transduction genetics, Swine, Trophoblasts cytology, Trophoblasts metabolism, Cell Differentiation genetics, Cellular Reprogramming genetics, Induced Pluripotent Stem Cells cytology, Pluripotent Stem Cells cytology
Abstract

We recently derived mouse expanded potential stem cells (EPSCs) from individual blastomeres by inhibiting the critical molecular pathways that predispose their differentiation. EPSCs had enriched molecular signatures of blastomeres and possessed developmental potency for all embryonic and extra-embryonic cell lineages. Here, we report the derivation of porcine EPSCs, which express key pluripotency genes, are genetically stable, permit genome editing, differentiate to derivatives of the three germ layers in chimeras and produce primordial germ cell-like cells in vitro. Under similar conditions, human embryonic stem cells and induced pluripotent stem cells can be converted, or somatic cells directly reprogrammed, to EPSCs that display the molecular and functional attributes reminiscent of porcine EPSCs. Importantly, trophoblast stem-cell-like cells can be generated from both human and porcine EPSCs. Our pathway-inhibition paradigm thus opens an avenue for generating mammalian pluripotent stem cells, and EPSCs present a unique cellular platform for translational research in biotechnology and regenerative medicine.

Published
2019
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2. Genome-Scale CRISPRa Screen Identifies Novel Factors for Cellular Reprogramming.

Author

Yang J, Rajan SS, Friedrich MJ, Lan G, Zou X, Ponstingl H, Garyfallos DA, Liu P, Bradley A, and Metzakopian E

Subjects
Animals, Biomarkers, CRISPR-Cas Systems, Cell Line, Gene Dosage, Germ Layers cytology, Germ Layers metabolism, Humans, Induced Pluripotent Stem Cells, Mice, Octamer Transcription Factor-3 genetics, Octamer Transcription Factor-3 metabolism, Pluripotent Stem Cells cytology, Pluripotent Stem Cells metabolism, Transcription Factors genetics, Transcription Factors metabolism, Cellular Reprogramming genetics, Clustered Regularly Interspaced Short Palindromic Repeats, Genome-Wide Association Study
Abstract

Primed epiblast stem cells (EpiSCs) can be reverted to a pluripotent embryonic stem cell (ESC)-like state by expression of single reprogramming factor. We used CRISPR activation to perform a genome-scale, reprogramming screen in EpiSCs and identified 142 candidate genes. Our screen validated a total of 50 genes, previously not known to contribute to reprogramming, of which we chose Sall1 for further investigation. We show that Sall1 augments reprogramming of mouse EpiSCs and embryonic fibroblasts and that these induced pluripotent stem cells are indeed fully pluripotent including formation of chimeric mice. We also demonstrate that Sall1 synergizes with Nanog in reprogramming and that overexpression in ESCs delays their conversion back to EpiSCs. Lastly, using RNA sequencing, we identify and validate Klf5 and Fam189a2 as new downstream targets of Sall1 and Nanog. In summary, our work demonstrates the power of using CRISPR technology in understanding molecular mechanisms that mediate complex cellular processes such as reprogramming., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2019
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3. Genome-Scale CRISPRa Screen Identifies Novel Factors for Cellular Reprogramming

Author

Yang, Jian, Rajan, Sandeep S, Friedrich, Mathias J, Lan, Guocheng, Zou, Xiangang, Ponstingl, Hannes, Garyfallos, Dimitrios A, Liu, Pentao, Bradley, Allan, Metzakopian, Emmanouil, Bradley, Allan [0000-0002-2349-8839], and Apollo - University of Cambridge Repository

Subjects
Pluripotent Stem Cells, epiblast stem cells, induced pluripotent stem cells, genome-wide screen, Gene Dosage, Article, CRISPR screen, Cell Line, Mice, Animals, Humans, Clustered Regularly Interspaced Short Palindromic Repeats, lcsh:QH301-705.5, CRISPR/Cas9, reprogramming pathways, lcsh:R5-920, gain-of-function, CRISPR activation, activation screen, reprogramming, Cellular Reprogramming, lcsh:Biology (General), embryonic structures, CRISPR-Cas Systems, lcsh:Medicine (General), Octamer Transcription Factor-3, Biomarkers, Germ Layers, Genome-Wide Association Study, Transcription Factors
Abstract

Summary Primed epiblast stem cells (EpiSCs) can be reverted to a pluripotent embryonic stem cell (ESC)-like state by expression of single reprogramming factor. We used CRISPR activation to perform a genome-scale, reprogramming screen in EpiSCs and identified 142 candidate genes. Our screen validated a total of 50 genes, previously not known to contribute to reprogramming, of which we chose Sall1 for further investigation. We show that Sall1 augments reprogramming of mouse EpiSCs and embryonic fibroblasts and that these induced pluripotent stem cells are indeed fully pluripotent including formation of chimeric mice. We also demonstrate that Sall1 synergizes with Nanog in reprogramming and that overexpression in ESCs delays their conversion back to EpiSCs. Lastly, using RNA sequencing, we identify and validate Klf5 and Fam189a2 as new downstream targets of Sall1 and Nanog. In summary, our work demonstrates the power of using CRISPR technology in understanding molecular mechanisms that mediate complex cellular processes such as reprogramming., Graphical Abstract, Highlights • Genome-scale CRISPRa screen in mouse EpiSCs identifies novel reprogramming factors • 50 novel genes, including Sall1 and Fam189a2, identified to mediate reprogramming • Sall1 synergizes with Nanog to increase reprogramming efficiency in EpiSCs and MEFs • RNA-seq provides insight into downstream pathways of Sall1 and Nanog-mediated reprogramming, In this study, Metzakopian and colleagues use CRISPR activation to perform a genome-scale reprogramming screen on mouse epiblast stem cells identifying 50 novel candidates. In addition, the authors provide evidence of Sall1 being a potent reprogramming gene, capable of synergizing with Nanog. Lastly, using RNA-seq, the authors provide insight into potential downstream targets of Sall1 and Nanog.

Published
2019

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